Analysis of the genetic basis of virus induced neoplastic disease has led to the identification of many chromosomal genes involved in these processes. Although most of these studies rely on use of the various inbred strains, we have begun to analyze a number of wild mice for infectious MuLVs and for susceptibility to virus induced disease. We have identified a novel infectious MuLV, termed HoMuLV, found in the European wild mouse M. hortulanus. HoMuLV has an ecotropic host range and induces neoplastic disease in NIH Swiss mice. HoMuLV was molecularly cloned and sequenced, and its gp70 and several gag proteins were shown to differ substantially from those of the known ecotropic MuLVs. In another series of experiments, we examined various wild derived mice which contained few copies of a single type of germline provirus for susceptibility to virus induced disease. In particular, M. spretus does not produce infectious virus nor does it express detectable levels of retrovirus-related RNA. However, this mouse produces infectious MCF recombinant virus 5 weeks after inoculation with MCF MuLV and develops lymphoma within 16 weeks. Thus, this mouse contains the endogenous sequences which can contribute to the generation of leukemogenic MuLVs. One germline spretus provirus has been molecularly cloned and is being characterized.